Assessment of causality of vaccine-induced adverse reactions

On Sept. 2013, the journal Vaccine published a paper co-signed by WHO’s experts and devoted to the causal assessment of adverse reactions following immunisation [1]. This paper attracted strong criticism, esp. from colleagues confronted with the hazards of immunisation programs the benefit/risk of which has not been properly assessed. I was asked by some to contribute, and my comment on this paper is now available on PubMed Commons; a copy is given below.

As a drug specialist with a more than 30-year experience in safety, I was often missioned as a medical expert witness in criminal or civil inquiries on vaccine litigations, where I repeatedly pointed out the worrying lack of knowledge of most vaccine experts regarding the basic scientific and regulatory requirements normally applicable to pharmaceutical products – esp. as far as adverse reactions were concerned: this represents a tragic shortcoming for such preventive drugs, targeted towards people in perfect health with the problematic aim of protecting them against diseases the occurrence of which in a severe form is often an unlikely event, and for which therefore the risk of side-effects should not go beyond extremely narrow limits…
Amongst many others examples, this paper by Tozzi et al. is an impressive illustration of this lack of expertise a far as drug safety is concerned.

Whatever the authors’ views on the matter, the primary tool to assess drug safety is not “epidemiological studies” but double-blind investigations versus placebo (a genuine placebo, namely a completely inert product and not another vaccine…) performed during development on a sufficient duration: as everybody knows, vaccine makers have managed the exploit to get exempted of this otherwise inescapable step. Additional indicators of amateurism in vaccine development include “fast track” procedures (whose consequences have been recently illustrated by the narcoleptic risk of Pandemrix), as well as the striking poverty of the dose-ranging studies (which account for regular turmoil in “experts” recommendations regarding the scheme of immunization as well as the timing of boosters).

As far as “epidemiological studies” are concerned, their main default is of being inextricably polluted by major conflicts of interests, as in most cases, they are performed either by the manufacturers or, even more frequently, by national or international health agencies (or their “experts”) whose most obvious interest is to hide the – sometimes tragic – drama they may have triggered by their irresponsible campaigns to promote some vaccines: this is the reason why, amongst a dozen of such studies performed on the neurological risks of hepatitis B vaccination, the only one showing a clear increase was also the sole whose financing was independent of any promoters of this immunization…

To come now to the assessment of causality of individual adverse reactions, the first remark is that the methodological inspiration of Tozzi et al. is regrettably obsolete. The use of algorithms has been almost completely abandoned by most regulatory bodies, for one reason which was pointed out more than 25 years ago [2]: namely, that use of algorithms (or decision table) is a tool for clinical decisions (e.g. to perform a laparotomy in view of such and such signs or symptoms), whereas assessing causality in drug toxicity is a process of knowledge, and not of decision (there is not the slightest signification in “deciding” whether a drug is, or not, the cause of an effect – and the reader has just to consider that this incredible way of reasoning is never used to assess drug efficacy, yet another pharmacological effect…). Lack of validation regarding the inter-raters agreement is an additional indicator of the methodological amateurism of the authors: this step should have been a strong prerequisite, taking account the vague of some items (e.g. that concerning an “appropriate time window after vaccine administration”, when experience of such an assessment with academic vaccine “experts” shows that it is almost invariably assessed as too short or too delayed… The same holds true for the item of “biological plausibility”, when experience, once again, teaches the fanatical obstinacy of most vaccine experts to challenge even the biological mechanisms which are most probable or convincing [3]).

Jacob Puliyel has listed a number of cases where Tozzi et al.’s algorithm would miss obvious vaccine causality. Let’s suggest another, that I witnessed in a number of sad instances: 3 weeks after a first injection, a person develops unexplained asthenia associated with paresthesia; one week after the second immunization, he/she develops motor symptoms, dysuria and visual disturbances; the day following the third injection, he/she is admitted to hospital where the diagnosis of multiple sclerosis is rapidly established. For any specialist in drug safety, the causal role of the vaccination would be highly probable: but not for Tozzi et al.…

Actually, amongst the 20 items of their checklist, no less than 15 (75%) are devoted to refute a vaccine-induced causality: no need to have read the Complete Psychological Works of Sigmund Freud to recognize the “resurfacing of the repressed” in such a bias. After all and as the authors confess with an astonishing ingenuousness, the main point is it not to “maintain public confidence in immunization programs”? Tell me: in any of the “immunization programs” – including those devised by vaccine makers (or their paid investigators) and for their sole sake [4]?...